Aberrant expressions of endometrial Id3 and CTLA-4 are associated with unexplained repeated implantation failure and recurrent miscarriage

Abstract

Inhibitor of DNA-binding protein 3 (Id3) is required for tumor angiogenesis and regulatory T-cell generation. However, the involvement of Id3 in unexplained repeated implantation failure (RIF) and recurrent miscarriage (RM) remains poorly understood. Immunohistochemistry was used to identify Id3, CD34, CTLA-4, and FOXP3 in the endometrium taken from the women with RIF (n=16), RM (n=16) and matched controls (n=8). The images were acquired and analyzed by the Vectra^® automated quantitative pathology imaging system. Percentage of Id3⁺ cells was significantly higher in the endometrium of women with RIF and RM compared with controls. The numbers of Id3⁺ and CD34⁺ vessels in the endometrium were positively correlated in control but not in RIF or RM. Percentages of CTLA-4⁺ cells, but not FOXP3⁺ cells, were significantly increased in the endometrium of RIF and RM women than those in controls. We found aberrant expressions of endometrial Id3 and CTLA-4 in peri-implantation endometrium of women with RIF and RM, suggesting the negative roles of these angiogenesis and immune tolerance markers involving in regulating endometrium receptivity.

Keywords: CD34; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); forkhead box P3 (FOXP3); inhibitor of DNA-binding protein 3 (Id3); recurrent miscarriage (RM); repeated implantation failure (RIF).